tbuckley/cabot-search huggingface dataset:
Effects of housing quality, housing stability, and contemporary mortgage lending bias on breast cancer stage at diagnosis among older women in the United States.
Authors: Nicole Rademacher, Yuhong M. Zhou, Emily L. McGinley, Purushottam W. Laud, Tina W.F. Yen, Sara Beltran Ponce, Ann B. Nattinger, Kirsten M. M. Beyer
Journal: Journal of Clinical Oncology (2022)

e18557 Background: The purpose of this study was to examine the association between measures of housing quality, stability, and access on breast cancer stage at diagnosis among older women living in the United States. Methods: This study included 67,588 women aged 66-90 with data from the SEER-Medicare linked database. The primary outcome was breast cancer stage at diagnosis. Multinomial regression models were performed using a three-category outcome (stage 0, early-stage (I-II), late-stage (III-IV)). The key independent variables were median housing value, percentage living in the same house as the previous year, percentage owner occupied homes, and an index of contemporary mortgage lending bias (redlining). Results: In adjusted models, higher contemporary mortgage lending bias was significantly associated with later-stage diagnosis (RR = 1.10 1.02-1.20; RR = 1.31, 95% CI 1.16-1.49; RR = 1.41, 95% CI 1.24-1.60 for Least to High, respectively). Median housing value was inversely associated with later-stage diagnosis, but to a lesser degree than mortgage lending bias (RR = 0.88, 95%CI 0.80-0.96; RR = 0.77, 95% CI 0.68-0.88 for second and third tertiles, respectively). Owner occupancy and tenure were not significantly associated with late-stage diagnosis in adjusted models. Conclusions: Contemporary mortgage lending bias demonstrated a significant dose-response relationship with later stage at diagnosis of breast cancer in this cohort of elderly women. Policy interventions aimed at reducing the effects of redlining with the goal of decreasing late-stage breast cancer diagnosis to improve prognosis should be considered. Table. Relative risk of late stage breast cancer diagnosis based on measures of housing quality and stability, as well as redlining. Risk is relative to the base outcome, stage 0. Values for the first tertile of housing quality and stability as well as the “least” category for redlining are not shown in this table as they are the base outcome which the other values are compared to. Standard error was adjusted for MSA clustering effects in all models.[Table: see text]
Prognostic value and therapeutic implications of an integrative molecular subtype and immune content classifier in localized muscle-invasive bladder cancer
Authors: M.F. Mark, B. Cotta, R. Vince, S. Nallandhighal, S. Kaffenberger, P. Palmbos, A.S. Alva, T. Morgan, G.S. Palapattu, S. Salami, A. Udager
Journal: European Urology (2022)
Association of Marital Status With Total and Cause-Specific Mortality in Asia
Authors: Chi Yan Leung, Hsi-Lan Huang, Sarah Krull Abe, Eiko Saito, Md. Rashedul Islam, Md. Shafiur Rahman, Ai Ikeda, Norie Sawada, Akiko Tamakoshi, Yu-Tang Gao, Woon-Puay Koh, Xiao-Ou Shu, Ritsu Sakata, Ichiro Tsuji, Jeongseon Kim, Sue K. Park, Chisato Nagata, San-Lin You, Jian-Min Yuan, Myung-Hee Shin, Wen-Harn Pan, Shoichiro Tsugane, Takashi Kimura, Wanqing Wen, Hui Cai, Kotaro Ozasa, Sanae Matsuyama, Seiki Kanemura, Yumi Sugawara, Aesun Shin, Keiko Wada, Chien-Jen Chen, Renwei Wang, Yoon-Ok Ahn, Habibul Ahsan, Paolo Boffetta, Kee Seng Chia, Keitaro Matsuo, You-Lin Qiao, Nathaniel Rothman, Wei Zheng, Daehee Kang, Manami Inoue
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Marital status has been shown to be associated with mortality, but evidence in Asian populations is limited. <h3>Objective</h3> To examine the association of marital status with total and cause-specific mortality. <h3>Design, Setting, and Participants</h3> This cohort study included individual participant data from 16 prospective studies in the Asia Cohort Consortium conducted between 1963 and 2015. Asian participants with complete information on marital and vital status were included. Study-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards model and then pooled using a random-effects meta-analysis. The analysis began in February 2021 and ended in August 2021. <h3>Exposures</h3> Marital status. <h3>Main Outcomes and Measures</h3> All-cause and cause-specific mortality. <h3>Results</h3> Of 623 140 participants (326 397 women [52.4%] and 296 743 men [47.6%]; mean [SD] age, 53.7 [10.2] years; mean [SD] follow-up time, 15.5 [6.1] years), 123 264 deaths were ascertained. Compared with married individuals, those who were unmarried had pooled HRs of 1.15 (95% CI, 1.07-1.24) for total mortality, 1.12 (95% CI, 1.03-1.22) for cerebrovascular disease mortality, 1.20 (95% CI, 1.09-1.31) for coronary heart disease mortality, 1.17 (95% CI, 1.07-1.28) for circulatory system diseases mortality, 1.06 (95% CI, 1.01-1.11) for cancer mortality, 1.14 (95% CI, 1.05-1.23) for respiratory diseases mortality, and 1.19 (95% CI, 1.05-1.34) for external causes of death. Positive associations with total mortality were also observed for those who were single (HR, 1.62; 95% CI, 1.41-1.86), separated (HR, 1.35; 95% CI, 1.13-1.61), divorced (HR, 1.38; 95% CI, 1.13-1.69), and widowed (HR, 1.09; 95% CI, 1.04-1.13). In subgroup analyses, the positive association persisted across baseline health conditions, and the risk of death was more pronounced among men or people younger than 65 years. <h3>Conclusions and Relevance</h3> This large pooled cohort study of individual participant data provides strong evidence that being unmarried, as well as belonging to the unmarried subcategories, was positively associated with total and cause-specific mortality. Investment of targeted social support services might need to be considered in light of the mortality differences between married and unmarried individuals.
Granzyme B+ CD4+ T cells associate with an unstable plaque phenotype in advanced human atherosclerosis
Authors: MAC Depuydt, V Smit, F Lozano Vigario, MNA Bernabe Kleijn, MR De Vries, PHA Quax, A Wezel, HJ Smeets, J Kuiper, AC Foks, I Bot, B Slutter
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Dutch Heart Foundation Cytotoxic CD4+ T cells have previously been found in peripheral blood of patients with coronary artery disease (1), however their occurrence in atherosclerotic plaques and their association with the pathophysiology of atherosclerosis has not been established. Single-cell RNA sequencing was performed on human carotid atherosclerotic plaques of 18 patients to identify specific T cell populations (2). Next, human femoral and carotid atherosclerotic plaques (n=95) and matched blood samples (n=49) were analyzed by flow cytometry for the presence of CD4+GZMB+ T cells. Plaque morphology was assessed by Movat’s Pentachrome staining. A distinct cytotoxic GZMB+ PRF1+ CD28- CD4+ T cell cluster was identified using single-cell RNA sequencing. Furthermore, flow cytometry analysis showed that the percentage of GZMB+CD4+ T cells was significantly elevated in plaque compared to blood (Blood: 12.17±2.0 vs. Plaque: 17.40±1.0; P=0.0002). Moreover, a significant positive correlation was observed between the percentage of GZMB+CD4+ T cells in blood versus plaque (P=0.031). In line with the proinflammatory character of these cells, we found a positive association of GZMB+CD4+ T cells (P=0.036) with necrotic core size, whereas no correlation was found with this subtype in the circulation. In this study we have shown an enrichment of cytotoxic CD4+ T cells in atherosclerotic lesions, which positively correlate with necrotic core size. Future studies are aimed at elucidating the role of these cells in advanced atherosclerosis.
Exploring the association between cardiovascular disease risk and gonadotropin releasing hormones agonists (GnRH) and prostate cancer diagnosis in men with type 2 diabetes mellitus: A nationwide, population-based cohort study
Authors: E. Lin, H. Garmo, B. Zethelius, E. Hagström, M. Van Hemelrijck, J. Adolfsson, P. Stattin, D. Crawley
Journal: European Urology (2022)
DIPG-35. Personalized treatment for molecularly heterogeneous Diffuse midline glioma, H3 k27-altered Paediatric case
Authors: Nahla Ali Mobark, Musa Alharbi, Yasser S Bayoumi, Aymn Albanyan, Ali Abdullah O Balbaid, Wael abdel Rahman Aljabarat, Malak Abedalthagafi
Journal: Neuro-Oncology (2022)

Abstract Diffuse midline glioma, H3 k27-altered (DMG) is a type of Paediatric- type diffuse high grade gliomas according to the 2021 WHO CNS tumors Classification. Diffuse intrinsic pontine glioma (DIPG) is another acceptable related term when it located in the pons with fatal prognosis. The combination of H3K27M with BRAF V600 mutations rarely reported in DMG although more commonly in Paediatric-type low grade gliomas (Diffuse low-grade glioma, MAPK pathway-altered). We present a twenty-month-old boy, previously healthy, presented with 2 weeks history of unsteady gait, drooling, cranial nerves palsy MRI imaging showed diffuse pontine mass with classic radiological features of DIPG. 2.6 x 1.6 x 3.2 (AP x TV x CC) with no evidence for spinal metastases. Patient underwent right retro sigmoid approach and open biopsy of lesion he received focal Radiation Therapy 54GY/30fx as stander of care of DIPG with mild neurogical improvement Pathological &amp; molecular Diagnosis was Diffuse midline glioma, H3 k27-altered with Co-occurrence BRAF V600E mutation. Two months after end of radiation, he presented with vomiting, and neurological deterioration with new right-side hemiplegia. Imaging studies showed interval increase in the pontine lesion with increased edema causing narrowing of the fourth ventricle, no active hydrocephalus. He was started on combination therapy BRAF inhibitor Dabrafenib and MEK Inhibitor Trametinib as maintenance therapy the patient gradually showed Marked neurological and clinical improvement. A 6-month MRI after start of targeted therapy showed favorable treatment response with complete resolution of the previous diffusion restriction, reduced tumor volume on MR perfusion ,reduced perilesional edema otherwise almost stabilization of nonenhancing pontine lesion. The poor prognosis of recurrent DIPG is well known but our patient is clinically and radiologically stable with excellent quality of life and well tolerating the therapy . Our case show that personalized treatment approach that address molecular heterogeneity of H3K27M glioma are safe and feasible
MEDB-49. Relapsed SHH medulloblastomas in young children. Are there alternatives to full-dose craniospinal irradiation?
Authors: Craig Erker, Brandon Craig, Simon Bailey, Maura Massimino, Valerie Larouche, Jonathan L Finlay, Cassie Kline, George Michaiel, Ashley Margol, Kenneth Cohen, Chantel Cacciotti, Virginia Harrods, Kathleen Doris, Mohammed AbdelBaki, Nisreen Amayiri, Zhihong Wang, Jordan Hansford, Juliette Hukin, Ralph Salloum, Lindsay Hoffman, Jeffrey Muray, Kevin Ginn, Zapotocky Zapotocky, Lorena Baroni, Vijay Ramaswamy, Stephen Gilheens, Dolli Aguiera, Claire Mazewski, Shafqat Shah, Douglas Strother, Sabine Muller, Amar Gajjar, Paul Northcott, Steve Clifford, Giles Robinson, Eric Bouffet, Lucie Lafay-Cousin
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND/RATIONAL: Following initial irradiation sparing therapy, many young children with relapsed medulloblastoma can be salvaged with craniospinal irradiation (CSI). However, the interval to relapse is short and neurocognitive sequelae remain a major concern. The contribution of molecular subgrouping may help refine indications and modalities of salvage strategies in this population. METHOD: From a cohort of 151 young children with molecularly characterized relapsed medulloblastoma, subset analysis of the SHH medulloblastoma was conducted to describe the practice of salvage radiotherapy and associated post-relapse survival (PRS). RESULTS: Sixty-seven SHH medulloblastoma patients (46 M0; 54 GTR; 11 non-ND/MBEN) received salvage therapy with curative intent. Before relapse, 54 (80.6%) received conventional chemotherapy (CC), 13 (19.4%) high-dose chemotherapy (HDC), while seven had additional focal radiotherapy (fRT). Median time to relapse was 11.1 months (range 3.8-41.0) and 43.3% were localized. Thirty patients (16 localized relapse) underwent surgery. Forty-seven (71.2%) received salvage radiotherapy (20 with CC; 10 with HDC; 15 alone, two unknown). CSI and fRT accounted for 82% and 18% respectively. CSI median dose was 36Gy (range 18-39Gy). Ten patients (eight with localized relapse) received CSI doses ≤23.4Gy. Nineteen patients (28.8%) did not receive any radiotherapy (nine HDC; 10 CC only). Radiotherapy was associated with better 3-year PRS (73.0% versus 36.1%; p=0.001). All patients treated with CSI ≤ 23.4Gy were alive at median follow-up of 69 months(24-142). Six of nine patients treated with HDC without irradiation were alive at last follow-up. Sixty-three percent of patients received reduced dose CSI(≤23.4Gy), fRT, or no radiotherapy, and their PRS did not significantly differ from those who received CSI ≥ 30.6Gy (p = 0.54). CONCLUSION: While salvage CSI provided PRS benefit in this SHH medulloblastoma cohort, we report the use of reduced salvage radiotherapy and irradiation avoidance in 63% of the patients, with 60% alive at last follow-up.
Tertiary care center experience: Functional and endoscopic results after aquablation in patients with benign prostatic hyperplasia-related lower urinary tract symptoms
Authors: D. Amparore, S. De Luca, S. De Cillis, E. Checcucci, G. Cattaneo, A. Pecoraro, A. Piana, F. Piramide, G. Volpi, M. Sica, P. Verri, S. Granato, S. Piscitello, M. Burgio, B. Carbonaro, J. Meziere, D. Zamengo, A. Quarà, E. Cisero, M. Della Corte, M. Manfredi, C. Fiori, F. Porpiglia
Journal: European Urology (2022)
Dapagliflozin alleviates left ventricular hypertrophy and cardiac dysfunction in mice
Authors: L Weber, PM Pilz, N Baumgartner, PL Szabo, Z Arnold, C Dostal, A Kiss, BK Podesser
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Ludwig Boltzmann Institute for Cardiovascular Research Introduction Sodium glucose cotransporter 2 inhibitors (SGLT2i) are a class of oral antidiabetic drugs. Recent clinical trials demonstrated and proved the cardiovascular benefit of SGLT2i in patients suffering from ischemic heart disease. In addition, left ventricular hypertrophy (LVH) is associated with cardiovascular events and using SGLT2i alleviated LVH in diabetic patients. However, only few studies investigated the effect of SGLT2i on regression of LVH in absence of diabetes. Aim of the study This study aimed to investigate whether the SGLT2i Dapagliflozin (DAPA) could attenuate LVH and cardiac dysfunction in a mouse model of pressure overload-induced LVH. Methods Male C57BL/6J mice (body weight 20-25g) were used. LVH was induced surgically by transverse aortic constriction (TAC). DAPA (1 mg/kg bodyweight/day) was administered through drinking water. The animals were divided in four groups: Group 1 underwent TAC for eight weeks (n=8). Group 2 concomitantly received DAPA for eight weeks after TAC (n=5). Group 3 received DAPA for only two weeks (in week 7 and 8 after TAC, n=5) to clarify if DAPA treatment could alleviate LVH at a later timepoint. Group 4 served as a sham control group (no LVH, n=8). Cardiac function was assessed using transthoracic echocardiography and invasive LV hemodynamic measurements. Results TAC resulted in a significant reduction in LV ejection fraction (LVEF) and significant increase in heart weight to body weight ratio (HW/BW) compared to sham (p&amp;lt;0.001). In addition, TAC mice showed a significant increase of LV systolic pressure and end-diastolic pressure compared to sham (p&amp;lt;0.01). Both the LVEF and LV functional parameters were markedly improved in mice treated with DAPA for eight weeks (p&amp;lt;0.05). LV mass decreased compared to the untreated group. More importantly, DAPA treatment for only two weeks also improved LVEF and alleviated LVH compared to untreated TAC mice (p&amp;lt;0.05). Furthermore, we also found that mice with only two weeks of DAPA treatment showed a tendency to improve LV hemodynamics. Conclusions DAPA was cardioprotective in a mouse model of pressure overload-induced LVH in absence of diabetes. It improved LV contractile function and LVH. DAPA also alleviated LVH and induced LV regression. Our findings uncovered that the SGLT2i DAPA contributed to the regression of LVH and cardiac fibrosis. Thus, administration of SLGT2i may be a novel adjunct therapy to boost reverse remodeling e.g. in patients with elective cardiac surgery and hypertrophic cardiomyopathy.
Electrical Impedance Tomography to Evaluate Sigh Effects in Unilateral Lung Injury
Authors: Luca Bastia, Martina Viganò, Carla Scattolini, Francesca Fossi, Federico Pozzi, Francesco Curto, Arturo Chieregato
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Electrical Impedance Tomography to Evaluate Sigh Effects in Unilateral Lung Injury." American Journal of Respiratory and Critical Care Medicine, 206(1), pp. 108–110
Size-tunable PEG-grafted copolymers as a polymeric nanoruler for passive targeting muscle tissues
Authors: Mitsuru Naito, Yusuke Watanuki, Kazuko Toh, Jongmin Yum, Beob Soo Kim, Kaori Taniwaki, Satomi Ogura, Hiroki Ishida, Masaru Cho, Hiroyuki Chaya, Ken Miyajima, Yuichi Yamasaki, Kensuke Osada, Katsura Minegishi, Yoshitsugu Aoki, Kanjiro Miyata
Journal: Journal of Controlled Release (2022)
The comparison of chemotherapy and treatments according to NGS results in advanced lung adenocarcinoma patients resistant to EGFR-TKIs.
Authors: Kan Jiang, Gen Lin, Xinlong Zheng, Xiaobin Zheng, Feng Long
Journal: Journal of Clinical Oncology (2022)

e21082 Background: There were no relative researches referring to optimal treatment strategy after the resistance to the first/second-generation EGFR-TKIs without T790M mutation or the third generation EGFR-TKIs as the first or second line therapy. Methods: Retrospective analysis was performed on the clinical and sequencing data obtained from 129 patients with advanced EGFR-mutant lung adenocarcinoma and disease progression on the prior EGFR-TKIs.The patients were divided into Chemotherapy group or Personalized group according the the therapies after acquired resistance to EGFR-TKIs. Results: 36 patients were enrolled in Personalized group and 93 in Chemotherapy group. Personalized group：22 patients with MET amplification received the combination therapy of EGFR-TKIs and MET inhibitors; 6 patients with SCLC transformation received EP/EC chemotherapy; 2 patients with BRAF mutation were treated with the combination of EGFR-TKIs, dabrafenib and trametinib; 3 patients with ERBB2 amplification were added Trastuzumab in the therapy; 2 patients with RET fusion were accepted LOXO-292 therapy; 1 patient had the combination therapy of the 1st and 3rd EGFR-TKIs because of T790m and C797S mutations in trans allelic context.Chemotherapy group: 79 patients received pemetrexed plus platinum therapy, 14 patients received paclitaxel plus platinum therapy. 12 patients achieved PR and 11 patients achieved SD in Personalized group, 48 PR, 25 SD in Chemotherapy group. The median PFS was 5.5 months in Chemotherapy group and 3.5 months in Personalized group, No significant differences were observed in ORR(p = 0.13), DCR(p = 0.12) and PFS(P = 0.26) between two group. Conclusions: Chemotherapy maybe is the optimal choice to patients with advanced EGFR-mutant lung adenocarcinoma and disease progression on the prior EGFR-TKI in current medical conditions.
ATRT-19. Functional genomics reveal distinct modulators of response to CDK4/6 inhibitors in ATRTs
Authors: Daniel Merk, Sohpie Hirsch, Foteini Tsiami, Bianca Walter, Lara Haeusser, Sepideh Babaei, Jakob Admard, Nicolas Casadei, Cristiana Roggia, Michael Spohn, Jens Schittenhelm, Stephan Singer, Ulrich Schüller, Federica Piccioni, Nicole Persky, David Root, Manfred Claassen, Marcos Tatagiba, Ghazaleh Tabatabai
Journal: Neuro-Oncology (2022)

Abstract Brain tumors are the leading cause of cancer-related deaths in children, and atypical teratoid rhabdoid tumors (ATRTs) are among the most common aggressive brain tumors in infants. With no standard-of-care treatment so far, ATRTs continue to have relatively low survival estimates, illustrating the urgent need for more efficacious treatment options. We have previously used genome-wide CRISPR/Cas9 knockout screens in combination with small-molecule drug assays to identify targetable vulnerabilities in ATRTs. CDK4/6 inhibitors, among the most promising drugs in our study with direct translational potential, are capable of inhibiting tumor growth due to mutual exclusive dependency of ATRTs on either CDK4 or CDK6. We here used genome-wide loss-of-function and gain-of-function strategies to identify modulators of response to CDK4/6 inhibition in ATRTs. Of note, while some well-known resistance mechanisms such as loss of RB1 or FBXW7 are shared by ATRT cell lines, we have also identified modulators of response to CDK4/6 inhibition with opposing effects across ATRT cell lines. As such, loss of AMBRA1, a recently described master regulator of D type cyclins, can either oppose the effects of or synergize with CDK4/6 inhibitors based on the cellular background. We are currently using a proteomics approach to further delineate the mechanism driving this functional heterogeneity of AMBRA1 in ATRTs. Our study will therefore provide deeper insights into the response of ATRTs to CDK4/6 inhibitors, which represent one of the most promising class of targeted agents for the treatment of ATRTs.
Lipid balance must be just right to prevent development of severe liver damage
Authors: Timothy F. Osborne, Peter J. Espenshade
Journal: Journal of Clinical Investigation (2022)

Nonalcoholic fatty liver disease (NAFLD) is a major health concern that often associates with obesity and diabetes. Fatty liver is usually a benign condition, yet a fraction of individuals progress to severe forms of liver damage, including nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Elevated sterol regulatory element–binding protein–driven (SREBP-driven) hepatocyte lipid synthesis is associated with NAFLD in humans and mice. In this issue of the JCI, Kawamura, Matsushita, et al. evaluated the role of SREBP-dependent lipid synthesis in the development of NAFLD, NASH, and HCC in the phosphatase and tensin homolog–knockout (PTEN-knockout) NASH model. Deletion of the gene encoding SREBP cleavage–activating protein (SCAP) from the liver resulted in decreased hepatic lipids, as expected. However, SCAP deletion accelerated progression to more severe liver damage, including NASH and HCC. This study provides a note of caution for those pursuing de novo fat biosynthesis as a therapeutic intervention in human NASH.
Testicular pain and YouTube™: Are uploaded videos a reliable source to get information?
Authors: A. Melchionna, C. Collà Ruvolo, M. Capece, R. La Rocca, G. Celentano, G. Califano, M. Creta, L. Napolitano, S. Morra, S. Cilio, C. Turco, V. Caputo, N. Longo, V. Mirone, C. Imbimbo
Journal: European Urology (2022)